EXCEED THE SPACE PROVIDED, This is a competitive renewal application for the Lowell P. Weicker Jr. General Clinical Research Center (GCRC), which was established at the University of Connecticut Health Center (UCHC) in December 1993. The GCRC is the key Center that supports and facilitates patient-oriented and translational research in medicine and dentistry at UCHC and its affiliates. It is chiefly an outpatient unit (>90%), in keeping with contemporary needs and pattems of use, but it also facilitates in-patient clinical research at UCHC and its affiliated hospitals. The GCRC provides an outstanding infrastructure with research nursing and study administration; core laboratory services, with increasing emphasis on genomics and molecular techniques; informatics; and biostatistics. It also provides excellent training opportunities in patie _;t-oriented research for medical and dental (and other) students, residents, fellows, and faculty. New ventures include further expansion of training, especially for students in the Medical Scientist Training Program, full implementation of data safety and monitoring plans by a research subject advocate, and establishment of a behavioral assessment core. This renewal application requests 5 years of support for 65 research protocols, compared to 36 in the last application. The emphasis in this application continues to be on studies involving collaboration and interact/ons among basic scientists and clinical investigators, particularly in the application of new methods of molecular biology and human genomics to the study of the pathogenesis and management of disease. The protocols in this renewal application cover a wide range, including studies on 1) alcohol and drug abuse, 2) osteoporosis and metabolic bone disease, 3) chronic hepatitis C and other liver diseases, 4) neuro/ogic changes associated with HIV, 5) neurologic complications of tick-borne infections, 6) genetics of schizophrenia, 7) pathogenesis of heart failure, 8) immunotherapy of cancer, 9) oral mucositis in bone marrow transplant patients, 10) treatment of scleroderma, as well as other research areas. The GCRC has become a major center for training. GCRC staff have refined the introductory course on methods of clinical research, developed a new course for training research coordinators, and now offer medical student electives. GCRC leaders and investigators have served as outstanding role models and mentors for junior investigators (CAP's, K-23 awardees and women's health scholars). UCHC continues to make a substantial commitment to support the GCRC by providing funding and infrastructure. Moreover, additional space has been provided to allow for expansion of our facilities. The UCHC GCRC has shown robust growth in clinical research activity and productivity. The proposed research will continue to enhance our understanding of pathogenesis and increase our ability to treat conditions that affect large numbers of Americans and other peoples throughout the world.